Lawrence Moon, King’s College, London, UK

Ribonucleases – a new target in SCI?

Funded in: 2014, 2015, 2016

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Problem: The ability of axons to produce key pro-regenerative factors is impaired after SCI as their encoding molecules (RNA) are destroyed by enzymes (RNases).

Target: Applying RNase inhibitors might dampen the destructive response of RNases.

Goal: A new candidate target for improving intrinsic re-growth capacity of axons.

Introduction: After spinal cord or brain injury, nerve fibers (“axons”) re-grow axons poorly over long distances. This is partly because they fail to produce key pro-regenerative factors from the molecules that encode them (“RNAs”).

Problem to be investigated: After spinal cord injury, axons might not re-grow long distances because many pro-regenerative RNAs are destroyed by enzymes called “RNases” (see panel A).

Methods: The team has discovered that injured neurons can be induced to regrow longer axons more rapidly when they genetically engineer injured neurons to contain increased levels of an “RNase Inhibitor” molecule. This new candidate therapy works by “caging” RNase enzymes that otherwise destroy RNA molecules (see panel B). This enables higher levels of important pro-regenerative molecules to be produced from their RNAs, resulting in faster, longer re-growth of injured nerve fibers.

Expected Results: The team now wishes to determine whether “RNase Inhibitor” promotes CNS axon regeneration and functional recovery in rats after spinal cord injury.

Potential Application: This might be a new candidate therapy for improving nerve fiber re-growth after SCI.